| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | ADVANCED SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-induced ATF3 expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells
1 Department of Functional Genomics, Medical Research Institute, and 2 Laboratory of Gene Expression, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Janpan
3 Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
ATF3 (Activating transcription factor 3), a member of the CREB/ATF family, can be induced by stress and growth factors in mammalian cells, and is thought to play an important role in the cardiovascular system. However, little is currently known about how the induction of ATF3 is regulated, except that the JNK pathway is involved. Here, we investigated the differential roles of the MAPK pathways involved in TNF
(tumour necrosis factor )-induced ATF3 expression in vascular endothelial cells. In human umbilical vein endothelial cells, the expression of constitutively active MKK7 (MAPK kinase 7) increased the number of ATF3-positive cells, and dominant negative MKK7 suppressed the TNF-induced expression of ATF3, indicating a requirement for the JNK pathway. In contrast, the expression of constitutively active or dominant negative MEK1/2 (MAPK/ERK kinase 1/2) suppressed or enhanced TNF-mediated induction of ATF3, respectively. In support of this, the MEK1/2 specific inhibitor U0126 enhanced the expression of ATF3 induced by TNF. Furthermore, the ERK pathway inhibits the TNF-mediated induction of ATF3 mRNA, but not its stability, suggesting the involvement of ERK activity in the transcriptional regulation of the ATF3 gene. Our results suggest that TNF-induced ATF3 gene expression is bidirectionally regulated by the JNK and ERK pathways in vascular endothelial cells.
Present address: Department of Physiology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, Shizuoka 431-3192, Japan.
* Correspondence: E-mail: m.hagiwara.end{at}mri.tmd.ac.jpThis article has been cited by other articles:
|
|
 |
|
  K.-H. Kim, J.-Y. Jeong, Y.-J. Surh, and K.-W. Kim Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes Nucleic Acids Res., January 1, 2010; 38(1): 48 - 59. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Inoue and Z.-G. Xiong Silencing TRPM7 promotes growth/proliferation and nitric oxide production of vascular endothelial cells via the ERK pathway Cardiovasc Res, August 1, 2009; 83(3): 547 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Mayer, V. Dexheimer, E. Nishida, S. Kitajima, and G. Thiel Expression of the Transcriptional Repressor ATF3 in Gonadotrophs Is Regulated by Egr-1, CREB, and ATF2 after Gonadotropin-Releasing Hormone Receptor Stimulation Endocrinology, December 1, 2008; 149(12): 6311 - 6325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Padmos, M. H. J. Hillegers, E. M. Knijff, R. Vonk, A. Bouvy, F. J. T. Staal, D. de Ridder, R. W. Kupka, W. A. Nolen, and H. A. Drexhage A Discriminating Messenger RNA Signature for Bipolar Disorder Formed by an Aberrant Expression of Inflammatory Genes in Monocytes Arch Gen Psychiatry, April 1, 2008; 65(4): 395 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. B. Kim, M. Kong, T. M. Kim, Y. H. Suh, W.-H. Kim, J. H. Lim, J. H. Song, and M. H. Jung NFATc4 and ATF3 Negatively Regulate Adiponectin Gene Expression in 3T3-L1 Adipocytes. Diabetes, May 1, 2006; 55(5): 1342 - 1352. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Lu, C. D. Wolfgang, and T. Hai Activating Transcription Factor 3, a Stress-inducible Gene, Suppresses Ras-stimulated Tumorigenesis J. Biol. Chem., April 14, 2006; 281(15): 10473 - 10481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Okamoto, Y. Iwamoto, and Y. Maru Oxidative Stress-Responsive Transcription Factor ATF3 Potentially Mediates Diabetic Angiopathy Mol. Cell. Biol., February 1, 2006; 26(3): 1087 - 1097. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Gomez, C. Gonzalez-Espinosa, S. Odom, G. Baez, M. E. Cid, J. J. Ryan, and J. Rivera Impaired Fc{epsilon}RI-Dependent Gene Expression and Defective Eicosanoid and Cytokine Production as a Consequence of Fyn Deficiency in Mast Cells J. Immunol., December 1, 2005; 175(11): 7602 - 7610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Xie, S. P. Bliss, T. M. Nett, B. J. Ebersole, S. C. Sealfon, and M. S. Roberson Transcript Profiling of Immediate Early Genes Reveals a Unique Role for Activating Transcription Factor 3 in Mediating Activation of the Glycoprotein Hormone {alpha}-Subunit Promoter by Gonadotropin-Releasing Hormone Mol. Endocrinol., October 1, 2005; 19(10): 2624 - 2638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. G. Bottone Jr., Y. Moon, J. S. Kim, B. Alston-Mills, M. Ishibashi, and T. E. Eling The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3) Mol. Cancer Ther., May 1, 2005; 4(5): 693 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Korcheva, J. Wong, C. Corless, M. Iordanov, and B. Magun Administration of Ricin Induces a Severe Inflammatory Response via Nonredundant Stimulation of ERK, JNK, and P38 MAPK and Provides a Mouse Model of Hemolytic Uremic Syndrome Am. J. Pathol., January 1, 2005; 166(1): 323 - 339. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | ADVANCED SEARCH | TABLE OF CONTENTS |
